MZB1-mediated IgA secretion suppresses the development and progression of colorectal cancer triggered by gut inflammation.

Colorectal cancer (CRC) ranks among the top causes of mortality globally. Gut inflammation is one crucial risk factor that augments CRC development since patients suffering from inflammatory bowel disease have an increased incidence of CRC. The role of immunoglobulin (Ig)A in maintaining gut homeostasis and preventing inflammation has been well established.

LAPTM5 mediates immature B cell apoptosis and B cell tolerance by regulating the WWP2-PTEN-AKT pathway.

Elimination of autoreactive developing B cells is an important mechanism to prevent autoantibody production. However, how B cell receptor (BCR) signaling triggers apoptosis of immature B cells remains poorly understood. We show that BCR stimulation up-regulates the expression of the lysosomal-associated transmembrane protein 5 (LAPTM5), which in turn triggers apoptosis of immature B cells through two pathways.

PPARδ is a regulator of autophagy by its phosphorylation.

In response to nutrient deficiency, autophagy degrades cytoplasmic materials and organelles in lysosomes, which is nutrient recycling, whereas activation of EGFR mediates autophagy suppression in response to growth factors. It is unclear whether PPARδ could be the regulator of autophagy in response to active EGFR. Here we found that EGFR induced PPARδ phosphorylation at tyrosine-108 leading to increased binding of LC3 to PPARδ by its LIR (LC3 interacting region) motif, consequently, inhibited autophagic flux.

INGs are potential drug targets for cancer.

Purpose: The inhibitor of growth (ING) family consists of ING1, ING2, ING3, ING4 and ING5, which function as the type II tumor suppressors. INGs regulate cell proliferation, senescence, apoptosis, differentiation, angiogenesis, DNA repair, metastasis, and invasion by multiple pathways. In addition, INGs increase cancer cell sensitivity for chemotherapy and radiotherapy, while clinical observations show that INGs are frequently lost in some types of cancers.

PPARα induces cell apoptosis by destructing Bcl2.

PPARα belongs to the peroxisome-proliferator-activated receptors (PPARs) family, which plays a critical role in inhibiting cell proliferation and tumorigenesis, while the molecular mechanism is still unclear. Here we report that PPARα serves as an E3 ubiquitin ligase to govern Bcl2 protein stability. PPARα physically bound to Bcl2 protein.